A Phase I, Safety Tolerability and Pharmacokinetics of AZD4831 to Treat Cardiovascular Disease

NCT ID: NCT03136991

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-15
• Study Completion Date: 2017-11-22

Brief Summary

This is a Phase I study to investigate the safety and tolerability of AZD4831 in healthy male participants, conducted at a single center. The results from this study will form the basis for decisions on future studies. Another purpose of this dose escalation study is to find out the right dose of the experimental drug to be given to study participants in future studies. Even though there were no harmful effects seen in the animals tested, investigator does not know what side effects the experimental drug might cause in humans. However, site personnel managing the study participants will be blinded to the extent possible and as long as possible to minimize any impact on data collection. Study participants will be blinded to treatment allocation.

The study will be conducted in healthy participants to avoid interference from disease processes or other drugs.

The participants will stay at the study center during the whole dosing period and until 48 hours post final dose.

Detailed Description

This is a Phase I study to investigate the safety and tolerability of AZD4831 in healthy male participants, conducted at a single center.The results from this study will form the basis for decisions on future studies. Another purpose of this dose escalation study is to find out the right dose of the experimental drug to be given to study participants in future studies. The study will be conducted in healthy participants to avoid interference from disease processes or other drugs. The participants will stay at the study center during the whole dosing period and until 48 hours post final dose.

Conditions

Cardiovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Cohort 1

Participants will receive AZD4831 5 mg/placebo oral suspension.

Group Type: ACTIVE_COMPARATOR

AZD4831

Intervention Type: DRUG

Participants will receive AZD4831 once daily, orally, for a period of 10 days. Note: Additional doses (for cohorts 2,3\&4) are provisional and could be adjusted based on the emerging data after the review of all available safety or other pertinent data from the previous dose by the Safety Review Committee (SRC).

Placebo

Intervention Type: DRUG

Participants will receive placebo matching the AZD4831 dose, once daily, orally, for a period of 10 days.

Cohort 2

Participants will receive AZD4831 (Additional dose 1)/placebo oral suspension.

Group Type: ACTIVE_COMPARATOR

AZD4831

Intervention Type: DRUG

Participants will receive AZD4831 once daily, orally, for a period of 10 days. Note: Additional doses (for cohorts 2,3\&4) are provisional and could be adjusted based on the emerging data after the review of all available safety or other pertinent data from the previous dose by the Safety Review Committee (SRC).

Placebo

Intervention Type: DRUG

Participants will receive placebo matching the AZD4831 dose, once daily, orally, for a period of 10 days.

Cohort 3

Participants will receive AZD4831 (Additional dose 2)/placebo oral suspension.

Group Type: ACTIVE_COMPARATOR

AZD4831

Intervention Type: DRUG

Participants will receive AZD4831 once daily, orally, for a period of 10 days. Note: Additional doses (for cohorts 2,3\&4) are provisional and could be adjusted based on the emerging data after the review of all available safety or other pertinent data from the previous dose by the Safety Review Committee (SRC).

Placebo

Intervention Type: DRUG

Participants will receive placebo matching the AZD4831 dose, once daily, orally, for a period of 10 days.

Cohort 4

Participants will receive AZD4831 (Additional dose 3)/placebo oral suspension.

Group Type: ACTIVE_COMPARATOR

AZD4831

Intervention Type: DRUG

Participants will receive AZD4831 once daily, orally, for a period of 10 days. Note: Additional doses (for cohorts 2,3\&4) are provisional and could be adjusted based on the emerging data after the review of all available safety or other pertinent data from the previous dose by the Safety Review Committee (SRC).

Placebo

Intervention Type: DRUG

Participants will receive placebo matching the AZD4831 dose, once daily, orally, for a period of 10 days.

Interventions

AZD4831

Participants will receive AZD4831 once daily, orally, for a period of 10 days. Note: Additional doses (for cohorts 2,3\&4) are provisional and could be adjusted based on the emerging data after the review of all available safety or other pertinent data from the previous dose by the Safety Review Committee (SRC).

Intervention Type: DRUG

Placebo

Participants will receive placebo matching the AZD4831 dose, once daily, orally, for a period of 10 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male participants aged 18 to 50 years (inclusive at Screening) with suitable veins for cannulation or repeated venipuncture.
• Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Presence of infection(s) (particularly fungal infection), as judged by the Investigator.
• History or current thyroid disease.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Any clinically significant abnormalities in biochemistry, hematology, or urinalysis results, as judged by the Investigator at Screening and/or Day 1, including

1. Alanine aminotransferase (ALT) not within normal range;

2. Aspartate aminotransferase (AST) not within normal range;

3. Creatinine not within normal range;

4. White blood cell (WBC) not within normal range;

5. Hemoglobin not within normal range; and

6. Estimated Glomerular Filtration Rate (eGFR) not within normal range.

• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) type 1 and 2.
• Abnormal vital signs, after 10 minutes supine rest, at Screening and/or Day 1, defined as any of the following:

1. Systolic BP (SBP) < 90 mmHg or ≥ 140 mmHg

2. Diastolic BP (DBP) < 50 mmHg or ≥ 90 mmHg

3. Pulse < 45 or > 85 beats per minute (bpm)

• Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or interventricular conduction delay with QRS > 110 ms. Participants with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of, for example, ventricular hypertrophy or pre-excitation at Screening and/or Day 1.
• Electrocardiogram findings suggesting a metabolic or other non-cardiac condition that may confound interpretation of serial changes (such as hypokalemia) at Screening and/or Day 1.
• Use of any prescribed or non-prescribed medication (other than paracetamol/acetaminophen), including antacids, analgesics, herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks before the first administration of IMP or longer if the medication has a long half-life.
• Plasma donation within 1 month of Screening or any blood donation/blood loss > 500 mL during the 3 months before Screening.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.
• Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Han, MD

Role: PRINCIPAL_INVESTIGATOR

California Clinical Trials Medical Group 1560 East Chevy Chase Dr., Suite 140 Glendale, CA 91206

Locations

Research Site

Glendale, California, United States

Countries

United States

Other Identifiers

D6580C00004

Identifier Type: -

Identifier Source: org_study_id